Cocaine dependence and other substance use disorders represent one of our society's most challenging and pressing health-related problems. These disorders are associated with increased risk for medical illness and injury, HIV exposure and AIDS, and frequently co-occur in those with other mental health problems. Thus, the need to better understand factors involved in the pathogenesis of cocaine use disorders is clear and compelling. Recent investigations indicate a strong association between stress and cocaine use. In a number of experimental paradigms, stress is associated with the initiation of or relapse to cocaine use. An estimated 43 percent of individuals with cocaine dependence meet lifetime criteria for comorbid posttraumatic stress disorder (PTSD), a psychiatric disorder which may develop following exposure to extreme stress. While the association between stress and cocaine use is well documented, little is understood about the mechanistic connection. The primary goal of this study is to investigate the role of stress reactivity in return to cocaine use among cocaine-dependent individuals with and without PTSD. Reactivity to experimentally induced stress will be assessed using both objective and subjective measures. Comprehensive evaluation of cocaine use will be conducted at one and four weeks post study entry. The specific aims are to: 1) compare stress reactivity between cocaine-dependent individuals with and without PTSD, 2) examine the relationship between physiologic stress reactivity and subsequent cocaine use, and 3) study the association between physiologic reactivity and cocaine craving. Careful study of the mechanistic link between stress, PTSD and cocaine dependence will inform existing theoretical models and may improve prevention and intervention efforts for this challenging patient population.